Mechanisms of the tolerance and homeostasis of immune cells

• Thesis title in Czech: Mechanismy tolerance a homeostáze imunitních buněk
• Thesis title in English: Mechanisms of the tolerance and homeostasis of immune cells
• Key words: Bardet-Biedl syndrom, T lymfocyty, adaptivní imunita, signalizace
• English key words: Bardet-Biedl Syndrom, T cells, adaptive immunity, signaling
• Academic year of topic announcement: 2017/2018
• Thesis type: dissertation
• Thesis language: angličtina
• Department: Department of Cell Biology (31-151)
• Supervisor: Mgr. Ondřej Štěpánek, Ph.D.
• Author: hidden - assigned by the advisor
• Date of registration: 17.10.2017
• Date of assignment: 17.10.2017
• Date of electronic submission: 18.02.2022
• Date of proceeded defence: 29.04.2022
• Opponents: prof. RNDr. Jan Černý, Ph.D.

Preliminary scope of work in English

BBSome is an octameric protein complex that facilitates trafficing of specific cargo proteins between cytosol and primary cilium. Mutations in BBSome subunits cause a severe multiorgan disease called Bardet-Biedl Syndrome (BBS). Because T cells do not form primary cilium, the role of the BBSome has not been addressed, yet. However, the immunological synapse, a contact site between a T cell and an antigen presenting-cell, exhibits some features of a primary cilium. For instance, proteins involved in ciliary trafficing, Rab8 and IFT20, are crucial for the polarization of T-cell antigen receptors towards the immunological synapse. Moreover, it has been shown that BBSome is required for targeting leptin receptor to the plasma membrane. Because leptin is an important modulator of T-cell biology, BBSome might play an important role in this regulatory pathway.
In this project, the applicant will analyze the immune system of a mouse model of BBS (BBS4 knock-out). She will focus on the development and function of lymphocytes using in vivo and in vitro models. In addition to the response to antigens, she will analyze selected signaling pathways (leptin, hedgehog, notch). To elucidate whether the observed phenotype is T-cell intrinsic, she will analyze also T-cell specific BBS4 knock-out driven by CD4-Cre. The applicant will take advantage of the models, techniques, and facilities available at the Group of Adaptive Immunity and at the Institute of Molecular Genetics (including transgenic mouse lines, Listeria monocytogenes infection, flow cytometry unit, microscopy, biochemical assays).